A program is outlined for studying the physiology and pharmacology of the colon of mice with hereditary megacolon and absence of enteric neurons. The objectives of the study are to determine: (1) How the electrical and mechanical activity of the pathological colon differs from the normal bowel. (2) What differences in the responses to electrical and mechanical stimuli of the colonic musculature exist between the abnormal and normal mice. (3) If differences in responses to autonomic drugs exist between normal mice and siblings with megacolon; if denervation hypersensitivity to drugs is present. (4) If the content and distribution of catecholamines, acetycholine, acetylcholine esterase, and certain metabolites differ in the aganglionic bowel. (5) The time course of development of the manifestations of fecal stasis and associated megacolon. (6) Etiology and pathophysiology of Hirschsprung's disease and related disorders of the alimentary canal.